Electroporation has evolved, over the past 15 years, as a viable in vivo DNA delivery method/technology. It has been investigated as a delivery method for DNA vaccines, cancer treatment, and the management of metabolic diseases with much success in preclinical studies. These applications have been translated into clinical trials; most of these are still ongoing. The primary complication of this method is controlling the application of direct current pulses so that the maximum or desired level, of expression is achieved in the target tissue. The complication arises from tissue to tissue variation and other factors which can result in under treating or over treating with electric pulses. Currently, no methods exist for controlling the application of pulses while they are being administered. This proposed study is designed to investigate the feasibility of using electrical impedance as a real time means of controlling the application of electroporative pulses. The study will first identify measureable tissue impedance changes that result from electroporative DNA delivery to skin. These changes will be used to develop a feedback algorithm that will work jointly with a pulse generator and impedance analyzer to control the application of electric pulses during the electroporation process. The system will be tested in a model for a secreted protein to determine if it can improve the resulting biological response/expression compared to applying electroporation in the standard manner. If successful, this study will demonstrate the feasibility of an improved manner for delivering DNA by electroporation to the skin. The results will be translatable to other tissues. PUBLIC HEALTH RELEVANCE: This study is relevant to public health as the results may lead to an improved method for delivering DNA based treatments for cancer, metabolic disorders, and immunotherapies. It will also be applicable for delivering DNA based vaccines.